Analysis of the prodiginine biosynthesis gene cluster of Streptomyces coelicolor A3(2):: new mechanisms for chain initiation and termination in modular multienzymes

被引:165
作者
Cerdeño, AM [1 ]
Bibb, MJ [1 ]
Challis, GL [1 ]
机构
[1] John Innes Inst, John Innes Ctr Plant Sci Res, Dept Microbiol & Mol Genet, Norwich NR4 7UH, Norfolk, England
来源
CHEMISTRY & BIOLOGY | 2001年 / 8卷 / 08期
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
antibiotic; fatty acid synthase; modular polyketide synthase; non-ribosomal peptide synthetase; Streptomyces;
D O I
10.1016/S1074-5521(01)00054-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Prodiginines are a large family of pigmented oligopyrrole antibiotics with medicinal potential as immunosuppressants and antitumour agents that are produced by several actinomycetes and other eubacteria. Recently, a gene cluster in Streptomyces coelicolor encoding the biosynthesis of undecylprodiginine and butyl-meta-cycloheptylprodiginine has been sequenced. Results: Using sequence comparisons, functions have been assigned to the majority of the genes in the cluster, several of which encode homologues of enzymes involved in polyketide, nonribosomal peptide, and fatty acid biosynthesis. Based on these assignments, a complete pathway for undecylprodiginine and butyl-meta-cycloheptylprodiginine biosynthesis in S. coelicolor has been deduced. Gene knockout experiments have confirmed the deduced roles of some of the genes in the cluster. Conclusions: The analysis presented provides a framework for a general understanding of the genetics and biochemistry of prodiginine biosynthesis, which should stimulate rational approaches to the engineered biosynthesis of novel prodiginines with improved immunosuppressant or antitumour activities. In addition, new mechanisms for chain initiation and termination catalysed by hitherto unobserved domains in modular multienzyme systems have been deduced. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:817 / 829
页数:13
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